2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung

BMC Pulm Med. 2010 Nov 7;10:56. doi: 10.1186/1471-2466-10-56.

Abstract

Background: Pseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).

Methods: We investigated 2-AA for its specificity to Ps. aeruginosa and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS).

Results: Cultures of 20 clinical strains of Ps. aeruginosa but not other respiratory pathogens had high concentrations of 2-AA in the head space of in vitro cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar® bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with Ps. aeruginosa 15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with Ps. aeruginosa 4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of Ps. aeruginosa in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in Ps. aeruginosa colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with Ps. aeruginosa (median 0, range 0-287; p < 0.003).

Conclusions: Our results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / analysis*
  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Breath Tests* / methods
  • Child
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / microbiology*
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Lung / microbiology
  • Male
  • Middle Aged
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / diagnosis*
  • Pseudomonas aeruginosa / chemistry*
  • Pseudomonas aeruginosa / growth & development
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / diagnosis
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Acetophenones
  • Biomarkers
  • 2-aminoacetophenone